Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis

• DOI: 10.1126/science.adn0327
• Publication Date: 2024-09-05T18:04:28Z
• Authors: Matthew D. Park; Jessica Le Berichel; Pauline Hamon; C. Matthias Wilk; Meriem Belabed; Nader Yatim; Alexis Saffon; Jesse Boumelha; Chiara Falcomatà; Alexander Tepper; Samarth Hegde; Raphaël Mattiuz; Brian Y. Soong; Nelson M. LaMarche; Frederika Rentzep...; Leanna Troncoso; Laszlo Halasz; Clotilde Hennequin; Theodore Chin; Earnest P. Chen; Amanda M. Reid; Matthew Su; Ashley Reid Cahn; Laura L. Koekkoek; Nicholas Venturini; Shira Wood-isenberg; Darwin D’souza; Rachel Chen; Travis Dawson; Kai Nie; Zhihong Chen; Seunghee Kim-Schulze; Maria Casanova-Ac...; Filip K. Swirski; Julian Downward; Nicolas Vabret; Brian D. Brown; Thomas U. Marron; Miriam Merad
• Keywords: Myelopoiesis; Senescence

Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. In this study, we establish that of the immune system, regardless age stroma and tumor, drives lung cancer progression. Hematopoietic enhances emergency myelopoiesis, resulting in local accumulation myeloid progenitor–like cells tumors. These are source interleukin (IL)–1⍺, which enhanced response. The age-associated decline DNA methyltransferase 3A IL-1⍺ production, disrupting IL-1 receptor 1 signaling early during development normalized myelopoiesis slowed growth lung, colonic, pancreatic human tumors, identified an enrichment IL-1⍺–expressing monocyte-derived macrophages linked to age, poorer survival, recurrence, unraveling promotes offering actionable therapeutic strategies.